Language：English   Publisher：Radiological Physics and Technology  

This study presents two cases of tumors in contact with the inferior vena cava during radiotherapy, and introduces a clinically useful technique for identifying tumor boundaries adjacent to blood vessels by adjusting the position of the field-of-view (FOV) to enhance the inflow effect in magnetic resonance imaging. We named this technique “Shifting-FOV.” This method consists of three steps: (1) remove the upper and lower saturation pulses outside the FOV, (2) align the FOV to position the lower edge of the imaging slab as close to the tumor as possible, and (3) manually adjust the table position to locate the tumor at the center of the magnetic field. The proposed method allowed for accurate identification of the tumor/vessel boundaries in both cases. This is a useful technique that can be readily applied to other facilities. Furthermore, images obtained using this technique may enable accurate tumor contouring in radiotherapy treatment planning.

DOI： 10.1007/s12194-023-00745-y

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Language：English   Publisher：Nagoya Journal of Medical Science  

Prostatic urethra identification is crucial in prostate stereotactic body radiotherapy (SBRT) to reduce the risk of urinary toxicity. Although computed tomography (CT) with a catheter is commonly employed, it is invasive, and catheter placement may displace the urethral position, resulting in possible planning inaccuracies. However, magnetic resonance imaging (MRI) can overcome these weaknesses. Accurate urethral identification and minimal daily variation could ensure a highly accurate SBRT. In this study, we investigated the usefulness of a three-dimensional (3D) T2-weighted (T2W) sequence for urethral identification, and the interfractional motion of the prostatic urethra on CT with a catheter and MRI without a catheter for implementing noninvasive SBRT. Thirty-two patients were divided into three groups. The first group underwent MRI without a catheter to evaluate urethral identification by two-dimensional (2D)- and 3D-T2W sequences using mean slice-wise Hausdorff distance (MSHD) and Dice similarity coefficient (DSC) of the contouring by two operators and using visual assessment. The second group provided 3-day MRI data without a catheter using 3D-T2W, and the third provided 3-day CT data with a catheter to evaluate the interfractional motion using MSHD, DSC, and displacement distance (Dd). The MSHD and DSC for the interoperator variability in urethral identification and visual assessment were superior in 3D-T2W than in 2D-T2W. Regarding interfractional motion, the Dd value for prostatic urethra was smaller in MRI than in CT. These findings indicate that the 3D-T2W yielded adequate prostatic urethral identification, and catheter-free MRI resulted in less interfractional motion, suggesting that 3D-T2W MRI without a catheter is a feasible noninvasive approach to performing prostate SBRT.

DOI： 10.18999/nagjms.85.3.504

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Language：English   Publisher：Clinical and Experimental Metastasis  

The prognosis and prognostic factors of patients receiving whole-brain radiotherapy (WBRT) for leptomeningeal metastasis (LM) from lung adenocarcinoma have not been established. Particularly, the impact of EGFR mutations and ALK rearrangements on survival remains unclear. This retrospective study evaluated the prognosis and prognostic factors of patients receiving WBRT for LM. We evaluated overall survival (OS) from WBRT initiation and clinical variables in 80 consecutive patients receiving WBRT for LM from lung adenocarcinoma at our institution between June 2013 and June 2021. After a median follow-up of 5.2 (range 0.5–56.5) months, the median OS was 6.2 months (95% CI 4.4–12.4). Of the 80 patients, 51 were classified as EGFR/ALK mutant (EGFR: 44; ALK: 6; both: 1) and 29 as wild-type. The median OS was 10.4 (95% CI 5.9–20.9) versus 3.8 (95% CI 2.5–7.7) months in the EGFR/ALK-mutant versus wild-type patients (HR = 0.49, P = 0.0063). Multivariate analysis indicated that EGFR/ALK alterations (HR = 0.54, P = 0.021) and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1 (HR = 0.25, P < 0.001) were independent factors associated with favorable OS. Among the patients who underwent brain MRI before and after WBRT, intracranial progression-free survival was longer in the 26 EGFR/ALK-mutant than 13 wild-type patients (HR = 0.31, P = 0.0039). Although the prognosis of patients receiving WBRT for LM remains poor, EGFR/ALK alterations and good ECOG PS may positively impact OS in those eligible for WBRT.

DOI： 10.1007/s10585-023-10225-7

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Language：English   Publisher：Journal of Neuro-Oncology  

Aim: This study aimed to investigate the clinical benefits of stereotactic radiosurgery (SRS) in patients with > 10 brain metastases (BM) compared to patients with 2–10 BM. Methods: The study included multiple BM patients who underwent SRS between 2014 and 2022, excluding patients who underwent whole brain radiotherapy, had a Karnofsky Performance Status score < 60, suspected leptomeningeal disease, or a single BM lesion. Patients were divided into two groups (2–10 and > 10 BM groups) and matched 2:1 based on propensity scores. The primary endpoint was overall survival (OS) in the matched dataset, with intracranial progression-free survival (PFS) as the secondary endpoint. Non-inferiority was established if the upper limit of the 95% confidence interval (CI) of the adjusted hazard ratio was below 1.3. Results: Of the 1042 patients identified, 434 met eligibility criteria. After propensity score matching, 240 patients were analyzed (160 in the BM 2–10 group and 80 in the > 10 BM group). The median OS was 18.2 months in the 2–10 BM group and 19.4 months in the > 10 BM group (P = 0.60). The adjusted hazard ratio was 0.86 (95% CI: 0.59–1.24), indicating non-inferiority. PFS was not significantly different between the groups (4.8 months vs. 4.8 months, P = 0.94). The number of BM did not significantly impact OS or PFS. Conclusions: SRS for selected patients with > 10 BM was non-inferior in terms of OS compared to those with 2–10 BM in a propensity score-matched dataset.

DOI： 10.1007/s11060-023-04358-8

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Language：English   Publisher：Nagoya Journal of Medical Science  

The local control rates of T1 bulky and T2 glottic carcinoma treated via radiation therapy alone are unsatisfactory; thus, we aimed to evaluate the efficacy and safety of our treatment protocol for early glottic carcinoma. Patients with early glottic squamous cell carcinoma treated via radiation therapy from January 2007 to November 2019 were reviewed. Patients were treated with: 63–67.5 Gy/28–30 fractions of radiation therapy alone for T1 non-bulky; concurrent chemoradiotherapy with S-1 and 60 Gy/30 fractions for T1 bulky and T2 favorable; and concurrent chemoradiotherapy with high-dose cisplatin and 66–70 Gy/33–35 fractions for T2 unfavorable glottic carcinoma. Local failure rates were estimated using the cumulative incidence function, overall and disease specific survival rates were estimated using Kaplan-Meier analysis, and adverse events were evaluated. Eighty patients were analyzed; the median age was 69.5 (range, 26–90) years, the median follow-up time for survivors was 40.1 (range, 1.9–128.4) months, and the 3-year local failure, disease specific survival, and overall survival rates were 5.8%, 98.3%, and 94.4%, respectively. In T1 bulky and T2 cases, the local failure rate was significantly lower in the concurrent chemoradiotherapy than in the radiation therapy alone group. Grade 3 acute dermatitis and mucositis were noted in nine and four patients, respectively. There were no acute adverse events of Grade 4 or higher, or late adverse events of Grade 2 or higher. The treatment protocol was effective and well-tolerated; thus, the efficacy of concurrent chemoradiotherapy was suggested in T1 bulky and T2 cases

DOI： 10.18999/nagjms.85.2.241

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Language：English   Publisher：Molecular and Clinical Oncology  

The present study aimed to assess the feasibility of global standard chemoradiotherapy (CRT) followed by surgery in patients with esophageal cancer. A prospective study was conducted at Nagoya University Hospital (Nagoya, Japan) to evaluate global standard CRT followed by surgery in patients with esophageal cancer. The CRT regimen consisted of 75 mg/m2 cisplatin on day 1 and 1,000 mg/m2 fluorouracil daily on days 1-4 given twice 4 weeks apart together with concurrent esophageal irradiation starting on day 1 (group A). For comparison, 17 patients with esophageal cancer who had received the same chemotherapy regimen but with lower drug doses were retrospectively reviewed: 70 mg/m2 cisplatin on day 1 and 700 mg/m2 fluorouracil daily on days 1-4 given twice 4 weeks apart together with concurrent esophageal irradiation starting on day 1 (group B). Grade 3 or worse adverse events were observed in 9 of the 12 patients (75%) in group A and in 5 of the 17 patients (29%) in group B. The patients in group A were more likely to experience grade 3 or worse neutropenia (50%) than those in group B (6%). No febrile neutropenia or treatment-related deaths occurred in either group. A total of 11 patients (92%) in group A and 16 patients (94%) in group B subsequently underwent an esophagectomy, and 9 (82%) and 14 (88%) of these patients, respectively, achieved microscopically margin-negative resection (R0 resection). In conclusion, global standard CRT was more likely to cause severe but manageable adverse events. There was no apparent difference in the R0 resection rate or postoperative complications between the two treatments. This clinical trial was registered at the Japan Registry of Clinical Trials (trial registration number: jRCT1041180004) on September 11, 2018.

DOI： 10.3892/mco.2023.2630

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Language：English   Publisher：Radiology  

Background: Changing iodinated contrast media (ICM) may reduce the risk of recurrent ICM-induced hypersensitivity reactions in patients with a prior reaction. Purpose: To perform a systematic review on the effectiveness of ICM change in comparison with no change to prevent recurrent ICM immediate hypersensitivity reactions. Materials and Methods: Multiple data bases were searched without language restriction between January 1990 and August 2021 to identify comparative studies of any design that included patients with a prior ICM hypersensitivity reaction to low-osmolality ICM and re-exposure to intravascular ICM. The methods used included a duplicate assessment of eligibility, double extraction of quantitative data, validity assessment, and random-effects meta-analysis. The primary outcome was the incidence of all-grade immediate recurrent hypersensitivity reactions. Secondary outcomes were the incidence of severe immediate recurrent hypersensitivity reactions and other adverse events associated with ICM change. Results: Six retrospective observational studies at moderate to severe risk of bias assessed 7155 adult patients (4329 in the ICM change group and 2826 in the no-change group). Studies adopted nonstandardized switching methods, and the proportions of the ICM change group ranged between 19% (five of 27 examinations) and 80% (3104 of 3880 examinations). A Bayesian meta-analysis revealed that changing ICM was associated with a reduced risk of recurrent hypersensitivity reaction by 61% (risk ratio = 0.39; 95% credible interval [CrI]: 0.24, 0.58). The wide-ranging estimates of risk reduction were not explained by the risk of bias ratings, the event rates in the no-change group, the index-reaction severity, or the co-administered nonstandard premedication. Rare severe recurrent reactions (five studies with five events) precluded a conclusion (risk ratio = 0.34, favoring ICM change; CrI: 0.01, 3.74). Adverse events associated with ICM change were not reported. Conclusion: In observational evidence of limited quality, iodinated contrast media (ICM)–change was associated with a reduced risk of recurrent immediate hypersensitivity reaction in patients with a prior ICM-induced hypersensitivity reaction.

DOI： 10.1148/radiol.220370

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Language：English   Publisher：Journal of Applied Clinical Medical Physics  

We aim to evaluate the basic characteristics of SRS MapCHECK (SRSMC) for CyberKnife (CK) and establish a dose verification system using SRSMC for the tumor-tracking irradiation for CK. The field size and angular dependence of SRSMC were evaluated for basic characterization. The output factors (OPFs) and absolute doses measured by SRSMC were compared with those measured using microDiamond and microchamber detectors and those calculated by the treatment planning system (TPS). The angular dependence was evaluated by comparing the SRSMC with a microchamber. The tumor-tracking dose verification system consists of SRSMC and a moving platform. The doses measured using SRSMC were compared with the doses measured using a microchamber and radiochromic film. The OPFs and absolute doses of SRSMC were within ±3.0% error for almost all field sizes, and the angular dependence was within ±2.0% for all incidence angles. The absolute dose errors between SRSMC and TPS tended to increase when the field size was smaller than 10 mm. The absolute doses of the tumor-tracking irradiation measured using SRSMC and those measured using a microchamber agreed within 1.0%, and the gamma pass rates of SRSMC in comparison with those of the radiochromic film were greater than 95%. The basic characteristics of SRSMC for CK presented acceptable results for clinical use. The results of the tumor-tracking dose verification system realized using SRSMC were equivalent to those of conventional methods, and this system is expected to contribute toward improving the efficiency of quality control in many facilities.

DOI： 10.1002/acm2.13645

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Language：English  

DOI： 10.7759/cureus.25888

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Internal Medicine  

<p><b>Objective </b>Few reports have described the real-world outcomes of rituximab, methotrexate (MTX), procarbazine, and vincristine (R-MPV) plus response-adapted whole-brain radiotherapy (WBRT) for elderly patients with primary central nervous system lymphoma (PCNSL). We evaluated the outcome of this regimen. </p><p><b>Methods </b>We evaluated >60-year-old patients with newly diagnosed PCNSL who received R-MPV plus WBRT from January 2010 to December 2019 at Toyohashi Municipal Hospital. The patients' characteristics, regimen enforcement, response rate, survival, and toxicity were analyzed. </p><p><b>Patients </b>Ten patients were consecutively enrolled. Their median age was 69 years old, and 60% had a performance status of 3 or 4 before induction therapy. </p><p><b>Results </b>Seven patients achieved a complete response after induction, and all 10 patients achieved a complete response after consolidation. Seven received reduced-dose WBRT at 23.4 Gy, and 2 received WBRT at 45 Gy. The median follow-up was 44.4 months; the 3-year progression-free survival and overall survival rates were 60% and 80%, respectively; and the cumulative incidence of relapse was 40%. The incidence of symptomatic delayed neurotoxicity was 70%. Of the 7 patients who received reduced-dose WBRT, 4 (57%) developed delayed neurotoxicity, including 1 severely affected patient. Only one patient survived without relapse and delayed neurotoxicity. The ratio of patients who developed relapse or delayed neurotoxicity that impaired daily life was 33% and 100% in the MTX high- and low-intensity groups, respectively. </p><p><b>Conclusion </b>This regimen in elderly patients is unsatisfactory because of delayed neurotoxicity. We should consider maintaining an adequate MTX intensity, postponing or minimizing WBRT, and choosing high-dose consolidation therapy for select patients. </p>

DOI： 10.2169/internalmedicine.7805-21

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CiNii Research

Language：English   Publisher：Nagoya Journal of Medical Science  

The Tokai Study Group for Therapeutic Radiology and Oncology (TOSTRO) started managing T1 glottic cancer using 2.25 Gy/fraction radiotherapy in 2011. The aim was to evaluate the local control (LC) rate and toxicity with 2.25-Gy radiotherapy in clinical practice and identify prognostic factors.The eligibility criteria were T1 glottic squamous cell carcinoma patients with age ≥20 years, treated with 2.25 Gy/fraction without chemotherapy between 2011 and 2017. LC rates were evaluated based on age, performance status, sex, T-category, tumor type (ulcerative or non-ulcerative), presence of anterior commissure invasion, tumor size, X-ray beam energy, and overall treatment time. Acute and late adverse events were evaluated using CTCAE version 4.0. A total of 202 patients were enrolled. The median follow-up period was 34.2 months. The 2 and 4-year LC rates were 93.8% and 93.1%, respectively. There was a significant difference in the LC rate between non-ulcerative type and ulcerative type (95.2% vs. 74.1% at 2 years, 94.4% vs. 74.1% at 4 years; p = 0.01). On univariate analysis, only tumor type was significantly correlated with a poor LC rate (hazard ratio 4.3; 95% confidence interval 1.2–15.4; p = 0.03). Acute grade 3 adverse events occurred in 17 patients. However, no late adverse events of grade 3 or higher have occurred to date. T1 glottic cancer treatment outcomes using hypofractionated radiotherapy with 2.25 Gy/fraction in clinical practice were comparable to previously reported results. However, ulcerative type tumor was associated with a poor LC rate.

DOI： 10.18999/nagjms.83.4.811

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Language：English   Publisher：BMC Cancer  

Background: Standard treatments for small cell carcinoma of the cervix (SCCC) have not been established. In this study, we aimed to estimate the optimal treatment strategy for SCCC. Methods: This was a multicenter retrospective study. Medical records of patients with pathologically proven SCCC treated between 2003 and 2016 were retrospectively analyzed. Overall survival (OS) was plotted using the Kaplan-Meier method. Log-rank tests and Cox regression analysis were used to assess the differences in survival according to stage, treatment strategy, and chemotherapy regimen. Results: Data of 78 patients were collected, and after excluding patients without immunohistopathological staining, 65 patients were evaluated. The median age of the included patients was 47 (range: 24–83) years. The numbers of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stages I-IIA, IIB-IVA, IVB were 23 (35%), 34 (52%), and 8 (12%), respectively. Of 53 patients who had undergone chemotherapy, 35 and 18 received SCCC and non-SCCC regimens as their first-line chemotherapy regimen, respectively. The 5-year OS for all patients was 49%, while for patients with FIGO stages I-IIA, IIB-IVA, IVB, it was 60, 50, and 0%, respectively. The 5-year OS rates for patients who underwent treatment with SCCC versus non-SCCC regimens were 59 and 13% (p < 0.01), respectively. This trend was pronounced in locally advanced stages. Multivariate analysis showed that FIGO IVB at initial diagnosis was a significant prognostic factor in all patients. Among the 53 patients who received chemotherapy, the SCCC regimen was associated with significantly better 5-year OS in both the uni- and multivariate analyses. Conclusion: Our results suggest that the application of an SCCC regimen such as EP or IP as first-line chemotherapy for patients with locally advanced SCCC may play a key role in OS. These findings need to be validated in future nationwide, prospective clinical studies.

DOI： 10.1186/s12885-021-08772-x

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OBJECTIVE: The purpose of this study was to determine the effectiveness of the combination of intraarterial and intravenous concurrent chemoradiation therapy (CIAIV-CCRT) for the treatment of high-risk uterine cervical cancer. METHODS: Between January 2000 and November 2004, we reviewed 45 cervical cancer patients treated by CIAIV-CCRT. The numbers of patients with stage IB2, IIA, IIB, IIIA, IIIB, and IVA were 3, 6, 14, 1, 17, and 4, respectively. Patients with stage III and IVA or patients with tumors >3 cm in diameter were enrolled in this study. Two sessions of CCRT were administered every 3 weeks using a combination of 70 mg/m2 x h(-1) cisplatin or 50 mg/m2 x h(-1) nedaplatin via the bilateral uterine artery and 2800 mg/m2 x 96 h(-1) 5-fluorouracil intravenously. Patients concurrently received external beam radiation therapy and brachytherapy. A nonrandomized control group of 47 patients who underwent radiation therapy alone between 1993 and 2000 was used for comparison. RESULTS: Of the 45 patients, 28 (62%) exhibited complete response and 16 (36%) exhibited partial response. One IIIB patient (2%) did not show any response. The 5-year overall survival (OAS) rates in the CCRT group and control group were 80.6% and 54.9%, respectively. With regard to late toxicities, no statistically significant differences were observed between the two groups. In uni- and multivariate analyses, positive pelvic lymph node showed a statistically significant influence on the OAS in the CIAIV-CCRT group (P = 0.049). CONCLUSION: These preliminary results suggest that CIAIV-CCRT can improve the prognosis of patients with high-risk cervical cancer.

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: We analyzed the therapeutic results and prognostic factors of 46 primary central nervous system lymphoma (PCNSL) patients who were treated at twelve institutions in the Tokai district of Japan between 1995 and 1999. We compared the results with those of a Japanese nationwide survey performed in the past. MATERIALS AND METHODS: We sent each institution a questionnaire about the state of patients' disease, pathological type, method and doses of radiotherapy, regimen and intensity of chemotherapy, and patients' prognoses. The range of patients' ages was 33 to 93 years (median, 61 years). Thirty-one were men and 15 were women. The most prevalent histology was diffuse large B cell type (33 patients). We used the Kaplan-Meier method to calculate the survival rate and Cox's proportional hazards model to analyze the prognostic factors. RESULTS: The five-year cumulative survival rate was 25%, and the median survival time was 22.7 months. The five-year disease-free survival rate was 23%. In monovariate analysis, patients who were both younger than 60 years old and had a WHO performance status (PS) score equal to or less than 2 showed a better survival rate. Furthermore, the patients receiving systemic chemotherapy showed a significantly better local control rate. In addition, patients who received systemic chemotherapy achieved a higher complete remission rate than those not receiving it. However, no factors that significantly influenced survival rate were identified in multivariate analysis. CONCLUSION: We demonstrated that the therapeutic outcome of PCNSL patients has recently improved. In particular, patients with good PS showed better local control than those with poor PS. However, we could not identify any significant prognostic factors in PCNSL patients.

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: The prognostic significance of human chorionic gonadotropin (HCG) level in central nervous system germinoma remains controversial. The purpose of this study was to compare clinical characteristics and prognosis of germinoma patients with normal and high HCG titers in the serum. METHODS AND MATERIALS: We undertook a multi-institutional retrospective analysis of 103 patients with central nervous system germinoma whose serum HCG and/or beta-HCG level had been measured before treatment between 1984 and 2002. All patients had been treated with radiation therapy either alone (n = 66) or in combination with chemotherapy (n = 37) with a median dose of 47.8 Gy. RESULTS: HCG and/or beta-HCG level in the serum was high in 39% of all patients. The proportion of HCG-producing tumors was higher in the lesions at the basal ganglia than in the lesions at the other sites. No correlation was found between tumor size and HCG level, but there seemed to be a weak correlation between size and beta-HCG. The 5- and 10-year survival rates were 96% and 94%, respectively, in both patient groups with normal and high HCG (p = 0.99). The 5- and 10-year relapse-free survival rates were 87% and 82%, respectively, in patients with normal HCG level and were both 87% in patients with high HCG (p = 0.74). Also, no other patient-, tumor-, or treatment-related factors seemed to influence the prognosis of the patients. CONCLUSION: Serum HCG level does not seem to influence patient prognosis when treated with sufficient doses of radiation. Relationship between tumor size and site and HCG level should be investigated further.

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: To investigate whether the prognosis of primary central nervous system lymphoma (PCNSL) patients treated by radiation alone remains still poor, we investigated the results of radiation monotherapy in the 1990s. METHODS AND MATERIALS: We collected data on 132 patients with histologically proven PCNSL treated by radiation alone in the 1990s. Follow-up data were updated as far as possible. Eleven patients who did not complete planned radiotherapy were included. The data were analyzed in relation to patient and tumor characteristics. The median patient age was 63 years, and the World Health Organization performance status (PS) was 3 or 4 in 40% of the patients. Multiple tumors were seen in 34%. Whole-brain irradiation with or without focal boost was used in 92%. The median radiation dose to the tumor site was 50 Gy (range, 8-74 Gy). RESULTS: For all 132 patients, the median survival time was 18 months and the 5-year survival rate was 18.0%. For 62 patients with PS 0-3 and aged 16-65 years (i.e., those eligible for the European Organization for Research and Treatment of Cancer 20962 study), the median survival was 26 months and 5-year survival was 24%. The 5-year survival was 25% for patients 63 years old or younger, and 9.8% for those older than 63 years (p = 0.0005). The 5-year survival was 22% for patients with PS 0-2 and 13% for those with PS 3 or 4 (p = 0.0040). Multivariate analysis confirmed the negative influence of higher age on patient prognosis. CONCLUSIONS: The results of radiation monotherapy for PCNSL appear to have improved as compared with those reported previously. The results of new treatment should be evaluated in light of this finding. Since most prospective studies on the combined treatment exclude poor PS and high-age patients, the 5-year survival rate of 30% may not be regarded as a marked improvement over radiation alone.

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Using a 21-in. cathode ray tube (CRT) monitor (2048 x 2560 x 8bits), six radiologists interpreted 12 images with interstitial lung disease under six conditions of CRT luminance (50 and 400 cd/m(2)) and room illuminance (20, 120 and 480lx), and 10 radiologists interpreted 25 images with pulmonary nodules under nine conditions of CRT luminance (50, 200 and 500 cd/m(2)) and room illuminance (20, 120 and 480lx). Observer's performance for interstitial disease was relatively better at 120lx. Four hundred and eighty lux illuminance with 50 cd/m(2) CRT luminance, which degraded the detectability of pulmonary nodule significantly (p<0.05), should be avoided for clinical use.

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Event date： 2023.4

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放射線治療の臨床について、症例提示を中心に講義した。